Human non-hematopoetic stem cells originating from the bone marrow and cord blood are increasingly used as mesenchyrnal cells for regenerative and immunemodulatory indications in patients. More than 80 clinical trials have been performed world-wide with mesenchymal stem cells.
Nearly all investigators use fetal bovine serum (FBS)-containing media as the standard serum supplement. FBS is of bovine origin, may transmit TSE (i.e., Transmissible Spongiform Encephalopathy) and stimulates immune responses in the recipient. Only BSE-free cattle are licensed by the authorities for use in humans (New Zealand) and investigators are engaged in efforts to develop alternative approaches for promoting cell growth. As cell-based therapies will likely be increasingly used in coming years, there will be an accompanying shortage of FBS.
Some companies have developed serum-free media. However, these media exhibit lower than ideal growth rates, and the morphology and the properties of bone marrow-derived CD34-negative stem cells in these media are not characterized as extensively as those in FBS-containing media.
Human thrombocytes (i.e., platelets) have been used by other investigators, as has Fresh Frozen Plasma (FFP), as growth-enhancing components. Platelets and their potential implications for regenerative medicine are reviewed separately by Stellos and Gawaz, and by Langer and Gawaz.
The following specific teachings in the art are noted with respect to stem cell expansion using platelets or FFP. Schallmoser, et al. discloses mesenchymal stem cell expansion using platelet lysate. Capelli, et al. discloses the use of non-filtered human platelet lysate to expand and produce mesenchymal stromal cells. Kocaoemer, et al. discloses the use of human AB serum and thrombin-activated platelet-rich plasma in expanding mesenchymal stem cells from adipose tissue. Muller, et al. discloses animal serum-free culture conditions for isolating and expanding multipotent mesenchymal stromal cells from human bone marrow, where these conditions employ both FFP and platelets. Blande, et al. discloses adipose tissue mesenchymal stem cell expansion in animal serum-free medium supplemented with autologous human platelet lysate that has been sterile filtered. Likewise, Salvadè, et al. discloses the use of platelet lysate in culturing mesenchymal stromal cells, wherein the lysate is sterile filtered.
Despite the known use of platelet lysate and FFP in culturing mesenchymal stem cells, there still exists an unmet need for a more rapid, cost-effective and safe way to culture such cells in a stable manner while preserving their ability to differentiate later when desired.